In 2015, the WHO African Region was responding to the largest Ebola virus disease outbreak in history while at the same time working to contain a wild poliovirus outbreak [1]. The 2030 Agenda for Sustainable Development had recently been endorsed, reflecting new global development priorities. By 2016, the Ebola outbreak was under control, and a new approach to reform and priority setting was in place in the region; the Transformation Agenda [2]. This agenda, introduced by the new Regional Director for Africa, Dr Matshidiso Moeti, set up a robust system for improving the efficiency and accountability of the WHO Secretariat for the African Region, which has been instrumental in the transformative changes that have been seen across the region in the past 10 years. This commentary discusses significant contributions to public health in the WHO African Region in the past decade, in the context of the Transformation Agenda, and the contributions of major investment in health security in the region. It is important to understand the need to sustain particular initiatives and elements of the transformative change that has taken place in the region.